The objective is to demonstrate rewarding properties of direct intracranial microinjections of abused drugs into the brain of the rat. The effects of experimenter-administered amphetamine, morphine or endorphin injections will be assessed on rate of lever-pressing for intravenous cocaine or heroin; if the microinjections are rewarding they should cause pauses in intravenous self-administration. Next it will be determined if intracranial microinjections will sustain lever pressing that was established and initiated under intravenous drug reinforcement. Finally we will attempt to train naive animals to lever-press for microinjection reinforcement. To determine if lever-pressing is really under the control of microinjection reinforcement we will compare lever-pressing rates of aimals that get microinjections only directly after lever-pressing with rates from animals that get the same microinjections in random relation to the time of lever-pressing. If true rewarding effects are seen we will try to localize them; sites of interest are nucleus accumbens, striatum, lateral hypothalamus and other catecholamine and endorphin/enkephalin terminal fields. Nearby sites will be tested. Local lesions will be made in attempts to eliminate pre- and post-synaptic lesions (6-OHDA and kainic acid) will be compared in their effects against apomorphine, amphetamine, morphine, enkephalin, endorphin, levorphanol and dextrorphan. Lesion extent will be estimated from nissl and silver stained material and by micropunch high-pressure liquid chromatography in the case of catecholamines. If rewarding effects of microinjections are found, and if they are reversible by localized lesions, we will then attempt to trace the circuitry linking the injection site to other systems, by injecting neuroanatomical tracers at the site. Horeseradish peroxidase will be used for retrograde and radiolabelled leucine will be used for orthograde tracing of sites synapsing at the injection site; systems critical for the rewarding drug effect will be determined by distal lesion studies.